5alpha-chloro-17alpha-ethynyl-19-nor-androstan-17beta-ol-3-one and method of preparation



United States Patent The present invention relates to a newcyclopentanophenanthrene derivative and to a process for the preparationthereof.

More specifically, the present invention relates to 50-chloro-17a-ethynyl-l9-nor-androstan-17,8-01-3-one and to a method forthe preparation of the same.

The compound object of the present invention is represented by thefollowing formula:

The compound represented by the above formula is a progestational andanti-ovulatory agent, useful in fertility control. Furthermore, it is ananti-estrogenic agent, inhibits the production of gonadotrophins andlowers the cholesterol level in the blood, adrenal glands and liver. Itis also useful in the treatment of premenstrual stress.

The new compound is prepared by the process illustrated by the followingequation:

In practicing the process outlined above, the starting compound17a-ethynyl-19-nor-testosterone (I), is dissolved in a small quantity ofa polar solvent inert to the action of dry hydrogen chloride, such aschloroform, methylene chloride, dioxane, etc., and treated with a streamof the aforementioned reagent, or with a solution of the same in asolvent of the type set forth above, thus producing5ot-Ch10lO-170t-6'thYI1yl-19-I10I-311d105t511-17,3-01-3-0118 (II). Tothose skilled in the art it is obvious that the dry hydrogen chloride orits solutions may be substituted by compounds which generate it in situ,such as for example, phosgene in the presence of moisture.

The following specific examples serve to illustrate the invention, butare not intended to limit its scope:

"ice

Example I A solution of 17a-ethynyl-19-nor-testosterone in cc. ofchloroform was cooled to 5 C. in an ice bath and then a stream of dryhydrogen chloride was introduced into the solution for 30 minutes. Theprecipitate formed was collected by filtration and washed withchloroform. The crude material thus obtained showed a melting point of198204 C. After recrystallizing the crude product from a large volume ofchloroform, there was obtained 50:-chloro-lh-ethynyl-l9-nor-androstan-l7;3-ol-3-one in pure form, with M.P.2l3214 C. (dec.); [a1 24 (dioxane).

Example II By following the process of the preceding example, but usingmethylene chloride instead of chloroform, there was obtained5u-chloro-l7a-ethynyl-l9-nor-androstan-l7fi-ol- 3-one, identical withthe produce of the preceding example.

Example III By the process described in Example I, but substituting thechloroform by dioxane, there was obtained the desired compound, whichexhibited the same physical constants.

Example IV By following the process of Example III, except that the dryhydrogen chloride was substituted by 10 cc. of a concentrated solutionof the same in dioxane, there was obtainedSat-chloro-17a-ethynyl-19-nor-androstan-l7,8-ol-3- one.

Example V By following the method of Example I, but substituting the dryhydrogen chloride by a chloroform solution of the same, there wasobtained the desired compound.

Example VI 17 a-ethynyl-l9-noratestosterone was treated in accordancewith Example I, except that the dry hydrogen chloride was substituted byphosgene, thus affording Sol-chloro-17a-ethynyl-l9-nor-androstan-17p-o1-3-one.

I claim:

1. A process for preparing 5otchloro-17a-ethynyl-l9-nor-androstan-17/3-ol-3-one which comprises reacting17aethynyl-l9-nor-testosterone in a polar organic solvent with dryhydrogen chloride.

2. The process of claim 1 wherein the solvent is chloroform.

3. The process of claim 1 wherein the solvent is methylene chloride.

4. The process of claim 1 wherein the solvent is dioxane.

5. The process of claim 1 wherein the hydrogen ch1oride is generated insitu by phosgene.

6. 5a-chloro-17a-ethynyl 19- nor-androstan-17p-ol-3- one.

References Cited in the file of this patent

1. A PROCESS FOR PREPARING5A-CHLORO-17A-ETHYNYL-19NOR-ANDROSTAN-17B-OL-3-ONE WHICH COMPRISESREACTING 17AETHYNYL-19-NOR- TESTOSTERONE IN A POLAR ORGANIC SOLVENT WITHDRY HYDROGEN CHLORIDE.